1. Field of the Invention
The present invention relates to a method of treatment of depression in a human being identified as having depression. This method comprises the administration of a therapeutically effective depression treatment amount of N-acetylserotonin (NAS) to a human being identified as having depression. NAS may be administered alone or in combination with other agents, e.g., Ca.sup.++ antagonists.
2. Background
Serotonin has been long ago considered to have the important role in the mechanism of antidepressant effect (see Lapin & Oxenkrug, 1969). Pineal gland has the highest concentration of serotonin in comparison with the other brain structures. Pineal serotonin is acetylated with the formation of N-acetylserotonin (NAS). NAS is further methylated by the hydroxy-indole-O-methyltransferase (HIOMT) to produce melatonin (5-methoxy-N-acetyltryptamine) (see Reiter, 1991). Melatonin exerted antidepressant-like activity in the "frog" test: potentiated the sedative effect of reserpine (Skene & Potgieter, 1981) and of selective MAO-A inhibitors (Requintina et al., 1994). We have recently observed the antidepressant-like activity of melatonin in the mouse tail suspension test (Prahie et al., in preparation). Selective MAO-A inhibitors (and some other antidepressants) stimulate the pineal NAS and melatonin production (Oxenkrug et al., 1994: see for rev. Oxenkrug, 1991). It was suggested that selective MAO-A inhibitors (and some other antidepressants) might correct the circadian rhythms abnormalities (and, thus, exert their antidepressant action) via their melatoninergic effects (Oxenkrug et al., 1986; see Oxenkrug, 1991).
Although NAS was viewed mainly only as an intermediate product of melatonin biosynthesis from serotonin, it was reported that some of its effects (i.e., hypothermic and analgesic) differed (qualitatively or quantitatively) from that of serotonin and melatonin (Morton, 1987; Psarakis et al., 1988).